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Molecular Pain 2016Whisker hair follicles are sensory organs that sense touch and perform tactile discrimination in animals, and they are sites where sensory impulses are initiated when...
Whisker hair follicles are sensory organs that sense touch and perform tactile discrimination in animals, and they are sites where sensory impulses are initiated when whisker hairs touch an object. The sensory signals are then conveyed by whisker afferent fibers to the brain for sensory perception. Electrophysiological property and chemical sensitivity of whisker afferent fibers, important factors affecting whisker sensory processing, are largely not known. In the present study, we performed patch-clamp recordings from pre-identified whisker afferent neurons in whole-mount trigeminal ganglion preparations and characterized their electrophysiological property and sensitivity to ATP, serotonin and glutamate. Of 97 whisker afferent neurons examined, 67% of them are found to be large-sized (diameter ≥45 µm) cells and 33% of them are medium- to small-sized (diameter <45 µm) cells. Almost every large-sized whisker afferent neuron fires a single action potential but many (40%) small/medium-sized whisker afferent neurons fire multiple action potentials in response to prolonged stepwise depolarization. Other electrophysiological properties including resting membrane potential, action potential threshold, and membrane input resistance are also significantly different between large-sized and small/medium-sized whisker afferent neurons. Most large-sized and many small/medium-sized whisker afferent neurons are sensitive to ATP and/or serotonin, and ATP and/or serotonin could evoke strong inward currents in these cells. In contrast, few whisker afferent neurons are sensitive to glutamate. Our results raise a possibility that ATP and/or serotonin may be chemical messengers involving sensory signaling for different types of rat whisker afferent fibers.
Topics: Adenosine Triphosphate; Animals; Electrophysiological Phenomena; Hair Follicle; Mechanotransduction, Cellular; Neurons, Afferent; Rats, Sprague-Dawley; Serotonin; Vibrissae
PubMed: 27927797
DOI: 10.1177/1744806916685570 -
The Journal of Physiology Jun 2020The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory...
KEY POINTS
The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory products of commensal gut bacteria can modulate the excitability of vagal afferent neurons with cell bodies in nodose ganglia. Cysteine proteases from commensal bacteria increased the excitability of vagal afferent neurons via activation of protease-activated receptor 2 and modulation of the voltage dependence of Na conductance activation. Lipopolysaccharide, a component of the cell wall of gram-negative bacteria, increased the excitability of nodose ganglia neurons via TLR4-dependent activation of nuclear factor kappa B. Our study identified potential mechanisms by which gut microbiota influences the activity of vagal afferent pathways, which may in turn impact on autonomic reflexes and behaviour.
ABSTRACT
Behavioural studies have implicated vagal afferent neurons as an important component of the microbiota-gut-brain axis. However, the mechanisms underlying the ability of the gut microbiota to affect vagal afferent pathways are unclear. We examined the effect of supernatant from a community of 33 commensal gastrointestinal bacterial derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) on the excitability of mouse vagal afferent neurons. Perforated patch clamp electrophysiology was used to measure the excitability of dissociated nodose ganglion (NG) neurons. NG neuronal excitability was assayed by measuring the amount of current required to elicit an action potential, the rheobase. MET-1 supernatant increased the excitability of NG neurons by hyperpolarizing the voltage dependence of activation of Na conductance. The increase in excitability elicited by MET-1 supernatant was blocked by the cysteine protease inhibitor E-64 (30 nm). The protease activated receptor-2 (PAR ) antagonist (GB 83, 10 μm) also blocked the effect of MET-1 supernatant on NG neurons. Supernatant from Lactobacillus paracasei 6MRS, a component of MET-1, recapitulated the effect of MET-1 supernatant on NG neurons. Lastly, we compared the effects of MET-1 supernatant and lipopolysaccharide (LPS) from Escherichia coli 05:B5 on NG neuron excitability. LPS increased the excitability of NG neurons in a toll-like receptor 4 (TLR )-dependent and PAR -independent manner, whereas the excitatory effects of MET-1 supernatant were independent of TLR activation. Together, our findings suggest that cysteine proteases from commensal bacteria increase the excitability of vagal afferent neurons by the activation of PAR .
Topics: Animals; Bacteria; Ecosystem; Gastrointestinal Microbiome; Mice; Neurons; Neurons, Afferent; Nodose Ganglion; Peptide Hydrolases; Vagus Nerve
PubMed: 32134496
DOI: 10.1113/JP279075 -
Biophysical Journal Apr 2017Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene...
Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/μm, and the tension was significantly decreased to ∼29 pN/μm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/μm by methyl-β-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions.
Topics: Actins; Animals; Cell Membrane; Cells, Cultured; Cytochalasin D; Cytoskeleton; Elasticity; Female; Ganglia, Spinal; Membrane Lipids; Microscopy, Electron, Scanning; Neurons, Afferent; Optical Tweezers; Peripheral Nervous System Agents; Rats, Sprague-Dawley; beta-Cyclodextrins
PubMed: 28445756
DOI: 10.1016/j.bpj.2017.02.040 -
American Journal of Physiology.... Mar 2015Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt...
Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.
Topics: Action Potentials; Animals; Anti-Obesity Agents; Appetite Depressants; Calcium; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Eating; Feeding Behavior; Hyperphagia; Injections, Intraperitoneal; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Neurons, Afferent; Obesity; Oxytocin; Proto-Oncogene Proteins c-fos; Sensory System Agents; Solitary Nucleus; Time Factors; Vagotomy; Vagus Nerve; Weight Gain
PubMed: 25540101
DOI: 10.1152/ajpregu.00344.2014 -
Nature Communications Sep 2018Spiral ganglion (SG) neurons of the cochlea convey all auditory inputs to the brain, yet the cellular and molecular complexity necessary to decode the various acoustic...
Spiral ganglion (SG) neurons of the cochlea convey all auditory inputs to the brain, yet the cellular and molecular complexity necessary to decode the various acoustic features in the SG has remained unresolved. Using single-cell RNA sequencing, we identify four types of SG neurons, including three novel subclasses of type I neurons and the type II neurons, and provide a comprehensive genetic framework that define their potential synaptic communication patterns. The connectivity patterns of the three subclasses of type I neurons with inner hair cells and their electrophysiological profiles suggest that they represent the intensity-coding properties of auditory afferents. Moreover, neuron type specification is already established at birth, indicating a neuronal diversification process independent of neuronal activity. Thus, this work provides a transcriptional catalog of neuron types in the cochlea, which serves as a valuable resource for dissecting cell-type-specific functions of dedicated afferents in auditory perception and in hearing disorders.
Topics: Animals; Cochlea; Hair Cells, Auditory; Hair Cells, Auditory, Inner; Neurons; Neurons, Afferent; Sequence Analysis, RNA; Single-Cell Analysis; Spiral Ganglion; Synaptic Potentials
PubMed: 30209249
DOI: 10.1038/s41467-018-06033-3 -
The Journal of Neuroscience : the... May 2023Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object...
Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object orientation at grip surfaces. We investigated how torque information is encoded by human tactile afferents in the fingerpads and compared them to 97 afferents recorded in monkeys ( = 3; 2 females) in our previous study. Human data included slowly-adapting Type-II (SA-II) afferents, which are absent in the glabrous skin of monkeys. Torques of different magnitudes (3.5-7.5 mNm) were applied in clockwise and anticlockwise directions to a standard central site on the fingerpads of 34 human subjects (19 females). Torques were superimposed on a 2, 3, or 4 N background normal force. Unitary recordings were made from fast-adapting Type-I (FA-I, = 39), and slowly-adapting Type-I (SA-I, = 31) and Type-II (SA-II, = 13) afferents supplying the fingerpads via microelectrodes inserted into the median nerve. All three afferent types encoded torque magnitude and direction, with torque sensitivity being higher with smaller normal forces. SA-I afferent responses to static torque were inferior to dynamic stimuli in humans, while in monkeys the opposite was true. In humans this might be compensated by the addition of sustained SA-II afferent input, and their capacity to increase or decrease firing rates with direction of rotation. We conclude that the discrimination capacity of individual afferents of each type was inferior in humans than monkeys which could be because of differences in fingertip tissue compliance and skin friction. We investigated how individual human tactile nerve fibers encode rotational forces (torques) and compared them to their monkey counterparts. Human hands, but not monkey hands, are innervated by a tactile neuron type (SA-II afferents) specialized to encode directional skin strain yet, so far, torque encoding has only been studied in monkeys. We find that human SA-I afferents were generally less sensitive and less able to discriminate torque magnitude and direction than their monkey counterparts, especially during the static phase of torque loading. However, this shortfall in humans could be compensated by SA-II afferent input. This indicates that variation in afferent types might complement each other signaling different stimulus features possibly providing computational advantage to discriminate stimuli.
Topics: Female; Humans; Torque; Touch; Fingers; Skin; Hand; Mechanoreceptors; Neurons, Afferent
PubMed: 37142429
DOI: 10.1523/JNEUROSCI.1305-22.2023 -
Science Advances Feb 2020Expression of the voltage-gated sodium channel Na1.7 in sensory neurons is required for pain sensation. We examined the role of Na1.7 in the dorsal horn of the spinal...
Expression of the voltage-gated sodium channel Na1.7 in sensory neurons is required for pain sensation. We examined the role of Na1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na1.7 knock-in mouse. Immuno-electron microscopy showed the presence of Na1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of Na1.7 in the dorsal horn. Peripheral nervous system-specific Na1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Na1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.
Topics: Animals; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials; Gene Expression; Immunohistochemistry; Mice; Mice, Knockout; NAV1.7 Voltage-Gated Sodium Channel; Posterior Horn Cells; Sensory Receptor Cells; Voltage-Gated Sodium Channel Blockers
PubMed: 32128393
DOI: 10.1126/sciadv.aax4568 -
Current Biology : CB Apr 2003The mechanism that allows a sensory neuron to extend its terminal branches along the appropriate fascicle within the CNS turns out to be the same as that which... (Review)
Review
The mechanism that allows a sensory neuron to extend its terminal branches along the appropriate fascicle within the CNS turns out to be the same as that which positioned the fascicle earlier on, and the gene that controls this position is the same as that which determined the neuron's identity.
Topics: Animals; Axons; Central Nervous System; Drosophila; Drosophila Proteins; Larva; Neurons, Afferent; Receptors, Immunologic
PubMed: 12676102
DOI: 10.1016/s0960-9822(03)00196-9 -
Neuron Jan 2004Insulin/IGF signaling has emerged as a central regulator of metazoan aging. In C. elegans, insulin-like peptides are expressed predominately in neurons. Alcedo and...
Insulin/IGF signaling has emerged as a central regulator of metazoan aging. In C. elegans, insulin-like peptides are expressed predominately in neurons. Alcedo and Kenyon demonstrate that removal of specific gustatory and olfactory neurons result in longer life, suggesting that metazoan longevity is influenced by sensory perception.
Topics: Animals; Longevity; Neurons, Afferent; Olfactory Receptor Neurons; Taste
PubMed: 14715127
DOI: 10.1016/s0896-6273(03)00839-0 -
Neuron Nov 2020As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict that complexity arises via...
As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict that complexity arises via convergent inputs from neurons with diverse response properties, in most vertebrate systems, convergence has only been inferred rather than tested directly. Here, we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. Strong, sparse synaptic inputs can be distinguished by their amplitudes, permitting analysis of afferent convergence in vivo. An independent approach, serial-section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Together, these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.
Topics: Animals; Electric Stimulation; Evoked Potentials, Somatosensory; Gene Knock-In Techniques; Microscopy, Electron; Neurons; Neurons, Afferent; Otolithic Membrane; Vestibular Nuclei; Zebrafish
PubMed: 32937099
DOI: 10.1016/j.neuron.2020.08.019